Immunology demystified: A guide for transplant hepatologists

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

Progresses in Integrated Traditional Chinese and Western Medical Research on Reproductive Immunology

Reproductive immunology is a crossed subject of reproductive biology and immunobiology. Great progresses have been achieved in the subject along with the deep development in life science. Modern reproductive immunology includes immunological regulation of fertility, materno-fetal immuno-regu-lation, and neuro-reproductive endocrino-immune network. With the integrated traditional Chinese and western medicine (ICWM) applied to reproductive immunology it has been greatly enriched in research contents and depth. The present review is to introduce the recent progresses in research of integrated medicine on reproductive immunology.

Old game, new players: Linking classical theories to new trends in transplant immunology

The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.

Role of the clinical immunology laboratory in disease monitoring

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

Bench-to-bedside strategies for osteoporotic fracture: from osteoimmunology to mechanosensation

Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery;however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Since the incidence of osteoporosis is expected to increase worldwide, orthopedic surgeons should pay more attention to comprehensive strategies for improving the poor prognosis of osteoporotic fractures. Herein, we highlight the molecular basis of osteoimmunology and bone mechanosensation in different healing phases of elderly osteoporotic fractures, guiding perioperative management to alleviate the unfavorable effects of insufficient mechanical loading, high inflammatory levels and pathogen infection. The well-informed pharmacologic and surgical intervention, including treatment with anti-inflammatory drugs and sufficient application of antibiotics, as well as bench-to-bedside strategies for bone augmentation and hardware selection, should be made according to a comprehensive understanding of bone biomechanical properties in addition to the remodeling status of osteoporotic bones, which is necessary for creating proper biological and mechanical environments for bone union and remodeling. Multidisciplinary collaboration will facilitate the improvement of overall osteoporotic care and reduction of secondary fracture incidence.

New insights into the immunology and evolution of HIV

Fewer than one million HIV infected individuals are currently receiving anti-retroviral therapy. Thelimitations of such treatment have underscored the need to develop more effective strategies to control thespread and pathogenesis of HIV. Typically, naturally occurring protective immune responses provide theparadigm for such development. It is now clear however that HIV can utilise the millieu of an activatedimmune system to its own replicative advantage. Mobilisation of the immune response, intended to thwartof HIV contributes to lack of immune control and the development of progressive disease in the majority ofinfected, untreated individuals. Further delineation of the intimate interactions between the HIV and theimmune system will be critical and recent advances in this direction are discussed.

《Cellular＆Molecular Immunology》杂志被SCI收录

由中国免疫学会主办、中国科学技术大学承办的英文免疫学会刊《Cellular＆Molecular Immunology》（www.cmi.ustc.edu.cn）创刊于2004年2月，在国内外各位专家和同仁的关注和中国免疫学会的全力支持下，该杂志已连续双月出版4卷；并先后被Chemical Abstracts，PubMed／MEDLINE等索引系统收录，在著名生物医学数据库PubMed／MENLINE检索系统中，国内外读者均可看到本刊所载文章的全文。

Cardiovascular Immunology Research in Wuhan Union Hospital:Over the Past 25 years

Cardiovascular immunology research in Wuhan Union Hospital began in 1991.Anti-heart antibodies in dilated cardiomyopathy and acute viral myocarditis began to be reported from 1993.It was found that a new autoantibody against L-type calcium channel results in ventricular tachycardia and sudden death in patients with dilated cardiomyopathy.Through the Intervention Study of Diltiazem in Dilated Cardiomyopathy,diltiazem was verifi ed to reduce mortality and the chronic heart failure hospitalization rate signifi cantly in patients with dilated cardiomyopathy.The autoantibodies against angiotensin II receptor type 1 andα1-adrenoceptor were associated with the increased recurrence of and death from stroke in hypertensive patients.Through many clinical and experimental studies,the functional imbalance of T-cell subsets was suggested to mediate myocardial injury and chronic heart failure,which provided a new theoretical basis for immunoregulation therapy for heart failure.The first antihypertensive polypeptide vaccine(ATRQβ-001)was invented.In addition to these achievements,there will be more research on cardiovascular immunology in Wuhan Union Hospital in the future.

Cancer immunology and immunotherapy

At the beginning of the last century,Dr.William Coley introduced“Coley’s toxin”to the scientific community after observing that a small number of patients with sarcoma with infections developed spontaneous tumor regression.“Coley’s toxin”consisted of bacteria or bacterial products and achieved a durable response in a small group of patients with cancer,most of whom had inoperable sarcoma.However,this response was usually unpredictable because of the lack of understanding of the immune response at that time.Since then,researchers have continued to study the relationship between cancer and the host immune system,and the discovery of“Coley’s toxin”marked the beginning of cancer immunotherapy^(1).

8th Sino-German symposium on immunology:fostering mutual trust and collaborative endeavors for advancing immunological science

The Sino-German Symposium on Immunology was jointly initiated by the Chinese Society of Immunology and the German Society of Immunology(DGFI)and was supported by the Sino-German Science Center of the National Natural Science Foundation of China.This symposium was the highest-level small-scale series forum between the two countries,and there have been eight successful sessions over the past 15 years.This series of forums promotes the continuous exchange of information and development of immunology between China and Germany through bilateral cooperation and joint training projects for young scholars.

Legacy of the discovery of the T-cell receptor: 40 years of shaping basic immunology and translational work to develop novel therapies

Forty years have passed since the groundbreaking achievement of cloning T-cell receptor genes [1, 2]. The rich narrative that sets the stage for this significant event is incredibly striking, and its profound legacy in contemporary immunology and medical science is truly remarkable.

Immunology of a unique biological structure:the Echinococcus laminated layer

The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species.The resulting diseases,collectively termed echinococcoses,include major neglected tropical diseases of humans and livestock.Echinococcus larvae are outwardly protected by the laminated layer(LL),an acellular structure that is unique to this genus.The LL is based on a fibrillar meshwork made up of mucins,which are decorated by galactose-rich O-glycans.In addition,in the species cluster termed E.granulosus sensu lato,the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate(Insp_(6)).The main purpose of our article is to update the immunobiology of the LL.Major recent advances in this area are(i)the demonstration of LL“debris”at the infection site and draining lymph nodes,(ii)the characterization of the decoy activity of calcium Inp6 with respect to complement,(iii)the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells(Clec4F),and(iv)the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages.Much information is missing on the immunology of this intriguing structure:we discuss gaps in knowledge and propose possible avenues for research.

Neuroimmunology:reviews and perspectives on recent advances

In an abstract sense,the immune system is tasked to monitor and interpret insults and potential threats from the external world and mount appropriate defensive actions accordingly.At the same time,it also monitors states of internal organs and facilitates resistance to perturbation and maintenance of homeostasis.

Lipid scrambling in immunology:why it is important

Asymmetric lipid distribution in the plasma membrane(PM)is one of the fundamental features of living cells.Lipids not only serve as structural components of the biophysical structure of the PM that preserves cell integrity but also participate directly in signaling.Acidic phospholipids(PLs),such as phosphatidylserine(PS),phosphatidylethanolamine(PE),and phosphoinositol(PI),are preferentially located in the inner layer of the PM,creating electrostatic charges for the docking of membrane-associated and cytoplasmic proteins carrying polybasic stretches of amino acids.However,there is emerging evidence that reversible changes in the distribution of these lipids take place in the PM and that these changes are critical for normal cell signaling,functions and homeostasis[1–3].They can also be implicated in the genesis of pathologies.

Liver immunology and its role in inflammation and homeostasis

The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor unresectable.The median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are necessary.Vascular resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal tumors.Thus,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.